Ask any manufacturer what process it uses to make inhalable drug particles, and the answer is likely to be micronization. This process has been the industry standard for decades, but it is not necessarily ideal. For starters, micronization is not well understood. In addition, a certain amount of material is lost during the process, so its final yield may not be optimal. Given these conditions, manufacturers have good reason to look for alternative processes for making inhalable medicines. Fortunately, several emerging methods show promise.

Particle replication in nonwetting templates

In 2005, researchers at the University of North Carolina (UNC) at Chapel Hill developed a technology called Particle Replication in Nonwetting Templates (PRINT). The method is based on the computer industry's procedure for making transistors, says Joseph DeSimone, professor of chemistry at UNC and leader of the research team. Using established technology, the researchers made etched silicon wafers to serve as templates for drug particles with previously determined characteristics. Using a template enables manufacturers to design the size and shape of their drug particles precisely, to target the upper airway or the alveolar sacs effectively, for example.

To scale up production, the team made a drum to pattern a print mold made of film that can be from 6 to 24 in. wide. The drum can make thousands of linear feet of molds, depending on the number of particles required.

After the molds are complete, their cavities are filled with the inhalable formulation, which can include the active ingredient alone or with excipients. Particles are harvested by adhesive films.

The PRINT technique, which complies with cGMP, can create traditional and large-molecule drugs for various diseases, including respiratory ailments such as cystic fibrosis and chronic obstructive pulmonary disease. The method also could be used to manufacture particles to fight bacterial infections or deliver chemotherapeutic agents to the lung. The researchers are interested in targeting the central nervous system through inhaled particles made using the PRINT process, says DeSimone.